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Publication Abstract from PubMed

Extracellular proteases are often produced as pre-pro-enzyme and then undergo multiple processing steps to mature into the active form. The protease Epp, a virulent factor of Vibrio anguillarum, belongs to this family. Its maturation might be regulated by Ca(2+) via its polycystic kidney disease (PKD) domain, but the molecular mechanism is unknown. Herein, we report the crystal structure of the first PKD domain from V. anguillarum Epp (Epp-PKD1) and its specific Ca(2+)-binding capacity. Epp-PKD1 exists as a monomer, consisting of seven beta-strands which form two beta-sheets stacking with each other. One Ca(2+) is bound by the residues Asn3, Gln4, Asp27, Asp29, Asp68 and a water molecule with a pentagonal bipyramidal geometry. Incubating the apo Epp-PKD1 with Ca(2+) but not Mg(2+), Mn(2+), or Zn(2+), enhances the thermal and chemical stability of Epp-PKD1, indicating its specific binding to Ca(2+). Epp-PKD1 shares high similarity in both sequence and overall structure with that of Vibrio cholerae PrtV, a homologous protease of Epp, however, they differ in the oligomeric state and local structure at the Ca(2+)-binding site, suggesting maturation of PrtV and Epp might be differently regulated by Ca(2+). Likely, proteases may take advantage of the structural diversity in PKD domains to tune their Ca(2+)-regulated maturation process.

Structural basis for specific calcium binding by the polycystic-kidney-disease domain of Vibrio anguillarum protease Epp.,Li P, Zang K, Li Y, Liu C, Ma Q Biochem Biophys Res Commun. 2018 Oct 28;505(2):471-477. doi:, 10.1016/j.bbrc.2018.09.108. Epub 2018 Sep 27. PMID:30268503^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.